inborn errors of metabolism 1

Question 1

Explain the genetic basis of IEMs and modes of inheritance

Answer 1

Inborn Errors of Metabolism - genetic disorders mostly involving single genes which code for enzymes involved inmetabolic pathways or transport proteins - clinical presentations usually arise due to accumulation of toxic substances or deficiency of product of metabolic pathway

Question 2

discuss the mtabolic consequences of impaired enzyme activity (IEM)

Answer 2

in an impaired enzyme situation

• accumulation of substrate
• deficiency of product
• diversion to alternate product

Question 3

list the categories of IEMs and discuss general clinical characteristics

Answer 3

Group 1= disorders which give rise to intoxication - accumulation of a toxic compound (PKU, MSUD, Organic acidurias) - generally they do not interfere with fetal development, most treatable with removal of toxin

Group 2= disorders involved in energy metabolism - IEM of intermediary metabolism and symptoms arise due to energy deficiency

Group 3= disorders involving complex molecues - involves cellular organelles including diseases associated with disturbed synthesis or catabolism of complex molecules (lysosomal storage disorder, etc)

Question 4

What is phenylketouria?

Answer 4

(Hyperphenylalaninaemia) -

deficiency of phenylalanine hydroxylase - so phenylalanine is made into phenylketones in the urine instead of making Tyrosine

these phenylketones can build up to highly toxic levels resulting in damage

Question 5

what is tyrosinaemia?

Answer 5

increased plasma concentration of tyrosine

Question 6

what is homocystinuria?

Answer 6

defect in cystathionine synthase - accumulation of homocysteine in the urine - methionine and metabolites elevated in the blood.

leads to mental retardation, osteoporosis, myocardial infarction and dislocation of the lens =

Question 7

what is maple syrup urine disease?

Answer 7

caused by a defect in the metabolism of leucine, isoleucine and valine - (deficiency in alpha keto acid dehydrogenase)

treatment = dietary restriction of branched chain amino acids

Question 8

discuss hyperammonaemia and disorders of the urea cycle including OTC deficiency

Answer 8

hyperammonaemia = high levels of ammonia in the blood which can be neurotoxic to CNS -

OTC deficiency leads to hyperammonaemia - due to deficiency of ornithine transcarbamylase enzyme

Question 9

describe the principles of newborn screening to detect inborn errors of metabolism

Answer 9

early detection of rare inherited conditions, before the onset of any clinical manifestations and the early introduction of treatment leads to better clinical outcome and avoids significant morbidity

we screen for (all of which ireland has a higher incidence of)

phenylketonuria

homocystinuria

maple syrup urine disease

classical galactosaemia

congenital hypothyroidism

cystic fibrosis

Question 10

What is Alkaptonuria?

Answer 10

deficiency in homogentisic acid oxidase

you see pigmentation of ears and eyes to a grey color